Frecuency of hereditary medullary thyroid carcinoma and RET proto-oncogen polymorphisms in patients with apparently sporadic medullary thyroid carcinoma.

SANSÓ G; VIEITES A; LEVIN G; BARONTINI M

New York City, NY. USA.

Congreso; LWPES/ESPE 8th Joint Meeting,; 2009

LWPES/ESPE , APEG, APPES, JSPE and SLEP

Medullary thyroid carcinoma (MTC) originates from C cells of the thyroid       and represents approximately 10% of all thyroid cancers. Approximately 75%       of all MTCs are believed to be sporadic, whereas the remaining 25%       correspond to inherited cancer syndromes. Little is known about the       etiology of sporadic MTC although previous reports suggest that the       presence of inherited genetic variants of Ret are associated with the       predisposition to or development of sporadic MTC. Several single       nucleotide polymorphisms of the RET gene have been described in the       general population as well as in patients with MTC. Aim: To evaluate the       incidence of hereditary disease in patients with apparently sporadic MTC       and to describe the frequency of inherited genetic variants in the RET       proto-oncogen. Patients and Methods: Screenig of Ret exons 10, 11, 13, 14       and 15 was performed by direct sequencing of DNA from 74 patients with       apparently sporadic MTC. The frequency of Leu769Leu (exon 13), Ser 804Ser       (exon 14) Ser904Ser (exon 15) and Gly691Ser (exon 11) polymorphisms was       studied in 36 of them. Results: 4/74 patients (5.4%) with apparently       sporadic MTC presented hereditary disease. The mutations found were:       Cys620Arg (2), Cys618Phe (1) and Cys634Tyr (1). 13/39 relatives (9> 20y       and 4< 20y) were studied. In seven of them the Ret mutation was detected.       36/74 patients were studied for polymorphisms and the allelic frequencies       were: 44.4% (16/36) Leu769Leu, 2 homozygous and 14 heterozygous, 33.3%       (12/36) Ser904Ser, 2 homozygous and 10 heterozygous, 50% (8/16) Gly691Ser,       3 homozygous and 5 heterozygous. All patients were negative for Ser836Ser.       Conclusions: The frequency of inherited disease that we found, among       patients with apparent sporadic MTC, strengthens the routine application       of Ret proto-oncogen DNA screening in all cases of this disease. The       frequency of Ret polymorphisms detected in these patients may suggest a       potential role of these variants in the development of sporadic MTC. A       putative role of the polymorphism as genetic modifier remains to be       established and further studies are necessary to characterize the clinical       behavior of MTC.